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Food Science and Human Wellness 5 (2016) 177–185

Research and development of Cordyceps in Taiwan

Ching-Peng Chiu a,1 , Tsong-Long Hwang b,c,d,1 , You Chan e , Mohamed El-Shazly f ,
Tung-Ying Wu g , I-Wen Lo a , Yu-Ming Hsu a , Kuei-Hung Lai a , Ming-Feng Hou h ,
Shyng-Shiou Yuan i , Fang-Rong Chang a,h,j,k,l,∗ , Yang-Chang Wu a,g,m,n,o,∗∗
aGraduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, China
b Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, China
c Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology,

Taoyuan 33302, Taiwan, China

d Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan, China
e Department of Microbiology and Immunology, and Institute of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung

40201, Taiwan, China

f Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
g Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 40402, Taiwan, China
h Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan, China
i Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, China
j Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, China
k Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, China
l Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, China
m Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 40402, Taiwan, China
n School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan, China
o Center of Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan, China

Received 2 May 2016; received in revised form 24 August 2016; accepted 30 August 2016
Available online 21 September 2016

Abstract
Cordyceps is treasured entomopathogenic fungi that have been used as antitumor, immunomodulating, antioxidant, and pro-sexual agent.
Cordyceps, also called DongChongXiaCao in Chinese, Yartsa Gunbu (Tibetan), means winter worm-summer grass. Natural Cordyceps sinensis
with parasitic hosts is difficult to be collected and the recent findings on its potential pharmacological functions, resulted in skyrocketing prices.
Therefore, finding a mass-production method or an alternative for C. sinensis products is a top-priority task. In this review, we describe current
status of Cordyceps research and its recent developments in Taiwan. The content and pharmacological activities of four major industrial species
of Cordyceps (C. sinensis, Cordyceps militaris, Cordyceps cicadae and Cordyceps sobolifera) used in Taiwan, were reviewed. Moreover, we
highlighted the effect of using different methods of fermentation and production on the morphology and chemical content of Cordyceps sp. Finally,
we summarized the bottle-necks and challenges facing Cordyceps research as well as we proposed future road map for Cordyceps industry in Taiwan.
© 2016 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Entomopathogenic fungi; Biofunction; Cordyceps sp.; C. sinensis; C. militaris; C. cicadae; C. sobolifera

∗ Corresponding author at: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, China.

Fax: +886 7 3114773.

∗∗ Corresponding author at: Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 40402, Taiwan, China.

Fax: +886 4 22060248.

E-mail addresses: aaronfrc@kmu.edu.tw (F.-R. Chang), yachwu@mail.cmu.edu.tw (Y.-C. Wu).
1 These authors contributed equally to this work.

Peer review under responsibility of Beijing Academy of Food Sciences

http://dx.doi.org/10.1016/j.fshw.2016.08.001
2213-4530/© 2016 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
178 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185

1. Introduction mushroom up to $32,000/kg justifying its name as “soft gold”

in China [10]. Cordyceps capsules in functional foods reached
Studies on medicinal mushrooms become a very impor- an average price of $5.8 per gram [11].
tant topic because of their potent pharmacological uses and Due to collection difficulties, most researchers invested in
huge global markets. Fungi form the second largest group after developing fermentation technologies to harvest large amounts
insects, and it is believed that 1.5 million fungi exist in nature [1]. of biomass for functional foods [12]. Functional foods can offer
They have attracted researchers from different disciplines owing health benefits and nutrition especially to an intended popula-
to their fascinating nature and capability to survive in hostile tion. In developed countries, chronic and age-related diseases
environments and the midst of decay at the harshest layer of the have turned into major causes of death. These kinds of foods,
ecosystem [2]. Different mechanisms in producing secondary which can protect or delay the onset of diseases such as cancer,
metabolites have been developed in various fungi from ancient diabetes mellitus, cardiovascular and obesity diseases, become
times till now. To human beings, these secondary metabolites a necessity rather than luxury [13].
are not only hazardous materials but also biofunctional agents In Taiwan, the origin of functional foods began in 1970 with
which were evolved over centuries with amazing potential in Taiwan Sugar Corporation, and has been developing over the
improving health and preventing diseases [3]. Currently, fungi last 40 years. People generally use functional foods to improve
materials can be obtained from two main sources, natural wild their stamina as well as to protect them from diseases. The
collection as well as artificial culture mycelium/fruity bodies. total global market value of functional food reached 896 billion
Collection of fungi from the wild is difficult and it raises seri- NTD (approximately 27 billion USD) in 2011 [14]. The most
ous concerns regarding environment sustainability; therefore, popular functional foods sold in Taiwan are herbal products,
most industrial manufacturers and academic research groups use functional drinks, and medicinal mushroom such as Agaricus
artificial fermentation technologies to obtain fungi material. blazei, Antrodia cinnamomea, Cordyceps sp., and Ganoderma
Mushrooms have been used by humans since thousands of lucidum. Additionally, dietary supplements such as multiple
years as food, functional food and/or folk medicine. More than vitamins, calcium tablets and glucosamine are widely used [15].
14,000 species of mushrooms are recognized, and among them, One of the most important features of functional foods econ-
approximately 2000 are identified as edible [4]. Other stud- omy is its resilience to economic recession. During 2008–2009
ies have suggested that many potential anticancer medicinal economic collapse, the sales of functional foods did not drop
mushrooms need to be developed, such as Agaricus, Antro- down but they increased due to high consumers’ satisfaction
dia, Albatrellus, Calvatia, Clitocybe, Cordyceps, Flammulina, and loyalty. Taiwanese consumers are interested in functional
Fomes, Funlia, Ganoderma, Inocybe, Inonotus, Lactarius, foods targeting metabolic, liver, sexual, and bone/joint disorders
Phellinus, Pleurotus, Russula, Schizophyllum, Suillus, Trametes [15]. In this review, we focus on the Cordyceos sp. functional
and Xerocomus, etc. [5]. The research evidences from various foods in Taiwan, including origins, chemistry, and biofunctions.
research groups all over the world demonstrated the beneficial This review aims to guide researchers for a better utilization of
therapeutic effects of mushroom extracts, and thus unarguably Cordyceos sp. in the development of new drugs and therapeutics
makes it a popular research area with mass attention. Certainly, targeting various ailments.
studying the rare and medicinally active mushroom, Cordyceps
sp., is included in this wave of research.
The entomogenous habit likely arose and spread concomi- 2. Studies on origins, chemistry and biofunctions
tantly with the diversification of phytophagous insects that
took place during the Cretaceous period [6]. Entomopathogenic 2.1. Cordyceps sinensis
fungi produce a wide range of secondary metabolites during
their infection and proliferation in insects [7]. Most ento- C. sinensis (Berk.) Sacc. is an entomopathogenic fungus that
mopathogenic fungi belong to the orders Entomophthorales has long been used as a Chinese medicine and tonic foods. The
and Hypocreales. Currently, 51 entomopathogenic fungi genera natural C. sinensis herbal product is composed of the fruiting
were identified with over 9000 isolates belonging to dif- body and its host larva. This species endophytically parasitizes
ferent species. These isolates are important and promising on dead caterpillars of the moth Hepilus spp. Spores of C. sinen-
bio-control agents for controlling arthropod pests [8]. Among sis geminate inside the caterpillars, filling the caterpillars with
the entomopathogenic fungi is the caterpillar fungus “Dong- hyphae, and produce a stalked fruiting body [16]. C. sinensis
ChongXiaCao”, which is an important Traditional Chinese exists in two stages: sexual stage (teleomorph) and asexual stage
Medicine (TCM). (anamorph). Generally, C. sinensis is similar to the sexual stage
The genus Cordyceps belongs to the Ascomycota, Pyreno- (teleomorph) with a caterpillar and fruiting body. In the past few
mycetes, Hypocreales, Clavicipitaceae. Cordyceps sp. are years, due to the high demand on C. sinensis, the collection of the
interesting macrofungi because of their characteristic parasitic fungus from its natural habitat has been insufficient, and so cul-
habitat on larvae and pupae of insects, and even on perfect insects turing C. sinensis as a conidial form (anamorphic stage) has been
[9]. Many natural Cordyceps sp. are used in traditional Chinese used as a substitute for the natural fruiting bodies [17]. However,
medicines in China, Japan, Korea, Taiwan and other eastern culturing C. sinensis does not produce a uniform mycelium and
Asian countries. In 2006, the imbalance between supply and the produced anamorphic type was named Hirsutella sinensis
demand of wild Cordyceps sinensis increased the price of the [18]. Genetic analysis of H. sinensis and C. sinensis proved that
 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185 179

both fungi are the same species but H. sinensis is the asexual solvent extracts of C. sinensis, containing nucleosides, sterols,
phase of the C. sinensis. fatty acids, etc., showed apoptotic and organ protective func-
Many compounds were purified from C. sinensis and their tions.
structures were elucidated using different spectroscopic tech-
niques. The isolated major compounds (Fig. 1) were cordycepin 2.2. Cordyceps militaris
(3 -deoxyadenosine, C10 H13 N5 O3 ), adenosine (C10 H13 N5 O4 ),
ergosterol (C28 H44 O), nucleosides and nucleobases [19–21]. Cordyceps militaris (bei-chong-cao, northern worm grass)
Adenosine containing extract from C. sinensis contributes to is a valuable source of a useful natural components possessing
the fungus hypotensive and vasorelaxant activities [22]. In order diverse biological activities. Despite some similarities between
to explore chemical components and biofunction of C. sinensis C. militaris and C. sinensis they differ in their color and host.
mycelia, the crude extract and partially purified fractions were The host of C. militaris is Lepidopteran pupa and the color of
examined for their inhibition ability of superoxide anion gen- its fruiting bodies is yellow or orange, while C. sinensis host is
eration and elastase release. Furthermore, five new compound, Hepialu larva, and the color of its fruiting bodies is dark brown.
cordysinins A–E were reported [23]. The sterol type compounds Scientists used electron microscopic tools such as TEM and
are important group in C. sinensis. Sterols H1-A from C. sinensis SEM to elucidate anamorph–teleomorph relationships of C. mil-
were isolated and purified by silica gel column chromatography itaris [29]. The examination indicated that providing a distinct
and high-performance liquid chromatography. They were found taxonomic name for the anamorph of C. militaris was unneces-
to suppress the active HMC (human mesangial cell) and alleviate sary for the practical purposes because this fungus is normally
IgAN (Berger’s disease) with clinical and histologic improve- dominant in nature as a teleomorph [30]. The fruiting bodies of
ment [24]. The study revealed that the pure compound H1-A may wild C. militaris are extremely expensive because of host speci-
be potentially useful for treating systemic lupus erythematosus ficity and rarity in nature. Also, they grow extremely slowly,
in patients [25]. It was suggested that H1-A might be effective in their growth is restricted to specific areas and their sizes are
the management of autoimmune disorders, apoptosis, and mod- very small. Consequently, the solid culture of C. militaris takes
ulation of signal transduction proteins, Bcl-2 and Bcl-XL [26]. a long time to provide fruiting bodies. Many attempts have been
C. sinensis contains a large amount of polysaccharides, which made to extract useful substances from the submerged mycelial
can be in the range of 3%–8% of the total weight and usually cultures to be incorporated in nutraceuticals and functional foods
comes from the fruiting bodies, the mycelium of solid fermen- [31]. Therefore, the collection of this fungus in large and suf-
tation submerged cultures and the broth [27]. Polysaccharides ficient quantities for the use as a drug remedy and in scientific
CME-1 exhibited highly potent antiplatelet activity that might research is an urgent priority. Many researchers tuned condi-
involve in the activation of adenylate cyclase/cyclic AMP and tions to culture this fungus, such as culture chemical components
subsequently the inhibition of intracellular signals such as Akt [32], illumination [33], gene expression [34] and traditional cul-
and MAPK resulting in the inhibition of platelet activation [28]. ture condition [35]. Batch to batch variations in fruiting bodies
The ancient herbal pharmacopoeia (Ben Cao Cong Xin) cultured products obtained under optimized conditions can be
recorded the activity of the mushroom in protecting “lung- monitored by a simple and rapid method using capillary elec-
kidney, resolving phlegm, hemostasis and improve erectile trophoresis (CE) and high-performance liquid chromatography
dysfunction”. According to the theory of TCM, the main effect (HPLC) [36]. Deep ocean water (DOW) was applied to culti-
of C. sinensis is enriching the lung yin and yang, which includes vate C. militaris in submerged and solid culture, and the effect
treating chronic lower back pain, sensitivity to cold, overabun- of DOW on the production of C. militaris fermentative products
dance of mucus and tears, chronic cough and wheezing, blood in was investigated. The results showed that it could significantly
phlegm from consumption of kidney yang (shenyangxu) [27]. C. increase the production of cordycepin [37]. In addition, the solid
sinensis also exhibited antibacterial function, reduced asthma, waste medium of C. militaris had been used for the prepara-
lowered blood pressure, and strengthened the heartbeat [27]. tion of cordycepin with high extraction efficiency and minimum
As highlighted in relevant citations, most reported bioactivities solvent usage [38]. The cultured and amplified fruiting bodies
were immunomodulatory, antiinflammatory, apoptotic (antitu- technologies applied to cultivate C. militaris were extremely
mor), and organ protective (lung and kidney) effects (Table 1). investigated and developed. The results of these investigations
In most studies, the treatment with C. sinensis water extracts are summarized in Table 2 showing their different morphological
brought immunomodulatory effect. On the other hand, organic characteristics.
Different chemical constituents from C. militaris were iso-
lated including polysaccharides, sugars, cerebroside derivatives,
sterols, nucleotides, nucleosides, proteins (cyclic dipeptides and
amino acid) and essential oils. In one report, authors demon-
strated the isolation of ten pure compounds from C. militaris
along with the evaluation of their biological activities by deter-
mining their effect on free radical NO and cytokines (TNF-␣ and
IL-12) production [39]. Among the isolated compounds cordy-
Fig. 1. Major chemical structures purified from Cordyceps sinensis. (A) Cordy- cepin, ergosterol, 3,4-O-isopropylidene-d-mannitol, d-mannitol
cepin, (B) adenosine and (C) ergosterol. and ergosterol peroxide showed the most potent activity through
180 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185

Table 1
Biological activities of C. sinensis extracts.
No. Extract or Material source Biological activity Mechanism pathway References
compound

1 Bailing capsule C. sinensis mycelium Renal protective Influenced SDF-1␣, CXCR4, [48]
CXCL12
2 Extract C. sinensis mycelium Hepatoprotective Reduced AST, TNF-␣,NO then [49]
increased IL-10 and SOD
3 Water extract Natural C. sinensis Hepatoprotective N/A [50]
4 Water extract C. sinensis mycelium Induce steroidogenesis Activated PKC [51]
5 Polysaccharide C. sinensis fruiting bodies Anti-tumor (U937) N/A [52]
6 Water extract C. sinensis mycelium Improve fertilization Increased P450 side chain cleavage [53]
enzyme, 3␤- hydroxysteroid
dehydrogenase and aromatase.
7 Supercritical C. sinensis mycelium Free radical scavenging and N/A [54]
carbon dioxide apoptotic (Hep 3B, Hep G2, HT-29
extract and HCT-116)
8 Supplementation C. sinensis mycelium Improve ergogenic value N/A [55]
9 95% alcohol C. sinensis mycelium Antidiabetic N/A [56]
extract
10. Water extract C. sinensis mycelium Antibacterial Increased IFN-␥, IL-12, p35, p40 and [57]
TNF-␣, but did not increase IL-1␤,
IL-6 or IL-8
11. Water extract C. sinensis mycelium Antibacterial Increased IL-12, TNF-␥and [58]
macrophage phagocytic activity
12 Methanol extract C. sinensis mycelium Radiation protective N/A [59]
13 Methanol extract C. sinensis fruiting bodies Immunomodulatory Suppressed IL-␤, IL-6, TNF-␣ and [60]
IL-8
14 Water extract C. sinensis mycelium Antiinflammatory Directed dendritic cells driven Th1 [61]
response toward a Th2 response.
15 Water extract C. sinensis mycelium Antiinflammatory N/A [62]
16 Methanol extract C. sinensis fruiting bodies Antiinflammatory and Inhibited NO, TNF-␣ and IL-12 [63]
antiproliferative
17 Water extract C. sinensis powder Immunosuppressant with C. sinensis N/A [64]
18 Freeze-dried C. sinensis fruiting bodies Antidiabetic N/A [65]
powder
19 Water extract C. sinensis mycelium Health supplement N/A [66]
20 Fraction of extract C. sinensis mycelium Increase steroid production N/A [67]
(F3)
21 Fraction of extract C. sinensis mycelium Stimulate in vivo testosterone N/A [68]
production
22 Protein of C. C. sinensis mycelium Stimulate the cAMP-PKA signal Activated cAMP-orotein kinase A [69]
sinensis transduction (regulate testosterone signal pathway, but did not activate
production) protein kinase C
23 Fraction of extract C. sinensis mycelium Stimulate in vivo and in vitro N/A [70]
testosterone secretion.
24 C. sinensis C. sinensis mycelium Affect transcription and translation N/A [71]
25 C. sinensis C. sinensis mycelium Activate PKA and PKC signal to Activated PKA and PKC signal [72]
stimulate steroidogenesis transduction pathway
26 C. sinensis C. sinensis mycelium Affect testosterone production N/A [73]
27 C. sinensis extract C. sinensis mycelium Does not induce StAR protein and/or N/A [74]
other protein expressions to stimulate
steroidogenesis
28 Water extract C. sinensis mycelium Does not induce in vivo N/A [75]
corticosterone production

N/A: not be mentioned in this article.

inhibiting inflammatory mediators production and human cancer [40]. The antiinflammatory activity of the isolated compounds
cell proliferation. Our group reported the purification of cere- was demonstrated by their inhibitory effect on the accumulation
broside, nucleotides and sterols from C. militaris fruiting bodies of pro-inflammatory iNOS protein and the reduction of COX-2
 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185 181

Table 2
Compare different characteristic of C. militaris and C. sinensis.
Properties Cordyceps militaris Cordyceps sinensis

Type

Stroma Plural Singular

Host Lepidopteran pupa Hepialus larva
Anamorphic Paecilomyces militaris Hirsutella sinensis
Distribute location Northeast of China Southwest of China
Artificial cultured Fruiting body & mycelium Mainly mycelium
Mycelium color White or yellow White
Fruiting body spores color Yellow or orange Dark brown
Major compound Cordycepin Adenosine

protein expression in LPS-stimulated RAW264.7 cells. This was An ergosterol proxide, 3␤-hydroxy-5,8-epidioxyergosta-
the first study reporting the isolation of cerebrosides with antiin- 6,22-diene (C28 H44 O3 ), from the Chan-hua exhibited
flammatory activity from this TCM. Another study reported the suppressant effects on T-cell proliferation, activated by PHA
identification of nonvolatile components of C. militaris fruiting [44]. Cordycepin was also reported to suppress NF-␬B through
bodies and mycelia [41]. The concentrations of the free amino Akt and p38 inhibition in RAW264.7 macrophage cells. A
acids in C. militaris fruiting bodies differed from mycelia. In a similar cordycepin derivative, N6-(2-hydroxyethyl)adenosine,
descending order, glutamic acid, cysteine, lysine, arginine and demonstrated antiinflammatory activity by suppressing
tyrosine were the major amino acids in the fruiting bodies. The TLR4-mediated NF-␬B signaling pathways [45]. In one
order differed in mycelia with tyrosine as the major amino acid previous report, myriocin, adenosine, cordycepin, N6-(2-
followed by lysine, cysteine and arginine. In general, these pre- hydroxyethyl)adenosine, ergosterol, ergosterol peroxides,
vious reports revealed that the chemical content and biological cyclic heptapeptides and polysaccharides were isolated from
activities of C. militaris cultured products differed with the cul- Chan-hua [43]. Based on Chan-hua literature, the mushroom is
ture conditions suggesting that uniform conditions are essential easy to be cultured and its chemical constituents are similar to
for stable products profile. those of C. sinensis. Therefore, it became another interesting
C. sinensis was used more extensively than C. militaris, nev- alternative for C. sinensis.
ertheless their clinical applications were similar. A number of The ancient herbal pharmacopoeia (Ben Cao Gang Mu) stated
valuable biological activities have been collected for C. mili- that Chan-hua can be used to treat “infantile convulsions and
taris by several teams (Table 3). It was revealed that C. militaris morbid night crying of babies, palpitation and malaria”. The
biological activities focused on antitumor, antidiabetic, anti- compendium of Materia Medica showed that C. cicadae relieved
inflammatory and improving sperm effects. These biological convulsion, dispelled wind and heat, promoted eruption and
activities are similar to those of C. sinensis rendering C. mil- improved eyesight, and removed eye. It also mentioned that C.
itaris as interesting alternative for the expensive and rare C. cicadae was primarily used in the treatment of infantile con-
sinensis. vulsions and morbid night crying of babies, palpitation and
malaria [43]. Literature had indicated that the two different
species of Cordyceps, C. sobolifera and C. cicadae, possess sim-
2.3. Cordyceps cicadae and Cordyceps sobolifera
ilar bioactivity. It is worth noting that three species (C. sinensis,
(Chan-hua)
C. sobolifera and C. cicadae) have a common characteristic in
renal protection effects [46]. Three different Cordyceps sp. were
Cordyceps cicadae and Cordyceps sobolifera are other
listed in the articles indicating the extent of the possible diver-
examples of entomogenous fungi belonging to the family
sity involved in the biology and activity. According to relevant
Clavicipitaceae and the genus Cordyceps. They are considered
references, the bioactivities of Chan-hua were described as anti-
two treasured traditional Chinese medicinal mushrooms known
inflammatory and renal protective effects (Table 4). In one recent
as Chan-hua, Sandwhe, and cicadae flower. They are rigorously
report, the possible health hazards arising from repeated expo-
parasitic on wingless Cicada nymphs or larva [42,43]. The mush-
sure to submerged mycelial culture of C. cicadae over 90 days
rooms absorb nutrition from larva and become a clover larva of
was investigated [47]. In general, Chan-hua possesses multi-
mycelium. The few fruiting bodies come out from the head,
ple pharmacological activities that provide featured advantages
mouth and bottom of the larva.
182 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185

Table 3
Biological activities of C. militaris extracts.
No. Extract or Material source Biological activity Mechanism pathway References
compound

1 Water extract C. militaris Antidiabetic Reduced the caspase-3 [76]

2 Water extract C. militaris fruiting body Antidiabetic Increased the IRS-1 and GLUT-4 [77]
3 C. militaris C. militaris fruiting body Antidiabetic Increased IRS-1, pIRS-1, AKT, [78]
and mycelium pAKT and GLUT-4
4 Methanol extract C. militaris fruiting body Antiinflammatory and anti-tumor Inhibited NO, TNF-␣ and IL-12 [79]
5 Water extract C. militaris mycelium Apoptotic (HL-60) N/A [80]
6 Fermentation C. militaris mycelium Anti-tumor N/A [81]
broth
7 Fermentation C. militaris mycelium Apoptotic (GBM8401) Involved to PI3K/Akt and MEK1 [82]
broth
8 Water extract C. militaris fruiting body Anti-asthma N/A [83]
9 Water extract C. militaris mycelium Anti-oxidative N/A [84]
10. Water extract C. militaris mycelium Hepatoprotective N/A [50]
11. C. militaris C. militaris mycelium Improve hormones and sperm Increased serum testosterone and [85]
supplement motility estradiol-17
12 C. militaris C. militaris mycelium Improve sperm production N/A [86]
supplement
13 Fermentation C. militaris mycelium Improve growth and mineralization N/A [87]
production

N/A: not be mentioned in this article.

Table 4
Biological activities of C. sobolifera and C. cicadae (Chan-hua) extracts.
No. Extract or compound Material source Biological activity Mechanism pathway References

1 Lipopolysaccharide C. sobolifera mycelium Improvement of renal function N/A [88]

2 Glycoprotein C. sobolifera mycelium Improvement of renal tubule function Increased the TRMP6 and TRMP7 [89]
channels
3 Polysaccharide C. sobolifera mycelium Improvement of renal function N/A [90]
4 Ergosterol peroxide C. cicadae fruiting body Antiinflammatory Suppressed T cell, cyclin E, IL-2, [91]
IL-4, IL-10, IFN-␥, c-Fos, c-Jun
5 N6-(2-Hydroxyethyl)- C. cicadae fruiting body Antiinflammatory Suppressed TLR4-mediated NF-␬B [92]
adensione signaling pathways
(HEA)
6 Methanol extract C. cicadae fruiting body Immunomodulatory Suppressed IL-2; IFN-␥ [93]

N/A: Not be mentioned in this article.

including low toxicity and the availability of inexpensive raw sis, C. militaris, C. sobolifera and C. cicadae (Chan-hua), have
materials from artificial cultivation. been developed as functional foods with profitable economic
value. Major active compounds of Cordyceps sp. were cordy-
3. Conclusion cepin and adenosine; however, the rest of potential compounds
need to be further investigated. Recently, we identified cerebro-
In this review, we selected four species of Cordyceps includ- sides as key components with potent anti-inflammatory activity
ing C. sinensis, C. militaris, C. sobolifera and C. cicadae [40]. So far, nucleosides, sterols, sugars, fatty acids and polysac-
(Chan-hua), which possess potent pharmacological activities charides were more often to be analyzed as quality markers of
and marketing potential. Literature indicated that these species Cordyceps. Among nucleosides, cordycepin and adenosine were
exhibited potent antitumor, antiinflammatory, lung-kidney pro- considered as important indicators in the chemical profiling of
tective effects. Interestingly, the major drive behind the use of Cordyceps sp. Furthermore, the Taiwanese traditional Chinese
these species is to improve stamina. medicine of pharmacopoeia indicated that adenosine was used
Literature reported approximately 500 species of medicinal in quality control protocols.
mushrooms in use. Among the most important genera are Antro- Moreover, different morphological or strain materials of
dia, Cordyceps Ganoderma and Phellinus, which are popular in Cordyceps genus are worthy of further development. Studies
the Taiwanese markets. Currently, four Cordyceps sp., C. sinen- on Cordyceps sp. should focus on developing this mushroom
 C.-P. Chiu et al. / Food Science and Human Wellness 5 (2016) 177–185 183

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